γ-Interferon alters globin gene expression in neonatal and adult erythroid cells

B. A. Miller, S. P. Perrine, G. Antognetti, D. H. Perlmutter, S. G. Emerson, C. Sieff, D. V. Faller

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Interferons have the ability to enhance or diminish the expression of specific genes and have been shown to affect the proliferation of certain cells. Here, the effect of γ-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant γ-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both (G)γ/(A)γ globin was decreased, since the (G)γ/(A)γ ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by γ-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in β-globin production occurred in cultures treated with γ-interferon. No toxic effect of γ-interferon on colony growth was noted. The addition of γ-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant α-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with γ-interferon results in an altered expression of globin genes. This supports the concept that developmental globin gene switching can be regulated by environmental factors.

Original languageEnglish (US)
Pages (from-to)1674-1681
Number of pages8
JournalBlood
Volume69
Issue number6
StatePublished - Aug 21 1987

Fingerprint

Erythroid Cells
Globins
Gene expression
Interferons
Fetal Hemoglobin
Gene Expression
Erythroid Precursor Cells
Erythroblasts
Fetal Blood
Blood
Genes
Liver
Bone
Hemoglobins
Bone Marrow
Developmental Genes
Radioligand Assay
Poisons
Granulocyte-Macrophage Colony-Stimulating Factor
Erythropoietin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Miller, B. A., Perrine, S. P., Antognetti, G., Perlmutter, D. H., Emerson, S. G., Sieff, C., & Faller, D. V. (1987). γ-Interferon alters globin gene expression in neonatal and adult erythroid cells. Blood, 69(6), 1674-1681.
Miller, B. A. ; Perrine, S. P. ; Antognetti, G. ; Perlmutter, D. H. ; Emerson, S. G. ; Sieff, C. ; Faller, D. V. / γ-Interferon alters globin gene expression in neonatal and adult erythroid cells. In: Blood. 1987 ; Vol. 69, No. 6. pp. 1674-1681.
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abstract = "Interferons have the ability to enhance or diminish the expression of specific genes and have been shown to affect the proliferation of certain cells. Here, the effect of γ-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant γ-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1{\%} of control cultures (erythropoietin only). Synthesis of both (G)γ/(A)γ globin was decreased, since the (G)γ/(A)γ ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by γ-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in β-globin production occurred in cultures treated with γ-interferon. No toxic effect of γ-interferon on colony growth was noted. The addition of γ-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6{\%} of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant α-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with γ-interferon results in an altered expression of globin genes. This supports the concept that developmental globin gene switching can be regulated by environmental factors.",
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Miller, BA, Perrine, SP, Antognetti, G, Perlmutter, DH, Emerson, SG, Sieff, C & Faller, DV 1987, 'γ-Interferon alters globin gene expression in neonatal and adult erythroid cells', Blood, vol. 69, no. 6, pp. 1674-1681.

γ-Interferon alters globin gene expression in neonatal and adult erythroid cells. / Miller, B. A.; Perrine, S. P.; Antognetti, G.; Perlmutter, D. H.; Emerson, S. G.; Sieff, C.; Faller, D. V.

In: Blood, Vol. 69, No. 6, 21.08.1987, p. 1674-1681.

Research output: Contribution to journalArticle

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AU - Miller, B. A.

AU - Perrine, S. P.

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AU - Faller, D. V.

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N2 - Interferons have the ability to enhance or diminish the expression of specific genes and have been shown to affect the proliferation of certain cells. Here, the effect of γ-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant γ-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both (G)γ/(A)γ globin was decreased, since the (G)γ/(A)γ ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by γ-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in β-globin production occurred in cultures treated with γ-interferon. No toxic effect of γ-interferon on colony growth was noted. The addition of γ-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant α-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with γ-interferon results in an altered expression of globin genes. This supports the concept that developmental globin gene switching can be regulated by environmental factors.

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Miller BA, Perrine SP, Antognetti G, Perlmutter DH, Emerson SG, Sieff C et al. γ-Interferon alters globin gene expression in neonatal and adult erythroid cells. Blood. 1987 Aug 21;69(6):1674-1681.